rs77009095

Variant names:

• chr5-78116244-C-T
• rs77009095
• NM_003664.5:c.1969-10G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003664.5(AP3B1):​c.1969-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,593,932 control chromosomes in the GnomAD database, including 4,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (326 hom., cov: 32)
  • Exomes 𝑓: 0.071 (3930 hom.)
• Consequence: AP3B1 NM_003664.5 intron
• Scores: Splicing: ADA: 0.0003659
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.179

Genes affected

AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 5-78116244-C-T is Benign according to our data. Variant chr5-78116244-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5	c.1969-10G>A		intron_variant	Intron 17 of 26	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2	c.1822-10G>A		intron_variant	Intron 17 of 26		NP_001258698.1
AP3B1	NM_001410752.1	c.1969-10G>A		intron_variant	Intron 17 of 22		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11	c.1969-10G>A		intron_variant	Intron 17 of 26	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8077 AN: 152090 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0660

GnomAD3 exomes AF: 0.0594 AC: 14856 AN: 250254 Hom.: 543 AF XY: 0.0619 AC XY: 8377 AN XY: 135408

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0374

Gnomad ASJ exome AF: 0.0893

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0556

Gnomad FIN exome AF: 0.0690

Gnomad NFE exome AF: 0.0785

Gnomad OTH exome AF: 0.0719

GnomAD4 exome AF: 0.0709 AC: 102280 AN: 1441724 Hom.: 3930 Cov.: 27 AF XY: 0.0711 AC XY: 51103 AN XY: 718722

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.0893

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0701

Gnomad4 NFE exome AF: 0.0777

Gnomad4 OTH exome AF: 0.0659

GnomAD4 genome AF: 0.0530 AC: 8073 AN: 152208 Hom.: 326 Cov.: 32 AF XY: 0.0529 AC XY: 3935 AN XY: 74414

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0541

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.0777

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0696 Hom.: 79

Bravo AF: 0.0514

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	1969-10G>A in intron 17 of AP3B1: This variant is not expected to have clinical significance because it has been identified in 7.5% (642/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs77009095). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hermansky-Pudlak syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2025

- -

Hermansky-Pudlak syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00037
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77009095; hg19: chr5-77412068;